Hildebrand B, Wissler B, Olenik C, Meyer D K
Department of Pharmacology and Toxicology, University of Freiburg, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1996 Oct;354(4):404-10. doi: 10.1007/BF00168429.
Meningeal fibroblasts express the proenkephalin gene during embryonal development but terminate the expression shortly before birth. When brought into primary culture at postnatal day 1, the fibroblasts again express the gene. Activation of protein kinase A reduces this expression and thus may contribute to its prenatal termination. Since the noradrenergic innervation of the meninges begins around the time of birth, it was investigated in the present study, how adrenergic agonists affected the levels of proenkephalin mRNA in cultured fibroblasts. The beta 2-adrenoceptor agonists salbutamol and procaterol increased the levels of endogenous cAMP and diminished the concentration of proenkephalin mRNA indicating that the cultured fibroblasts possessed this beta-subtype. In contrast, noradrenaline increased the level of proenkephalin mRNA in a concentration-dependent manner. This effect was independent of endogenous cAMP and was mediated by alpha 1-adrenoceptors. The data indicate that the noradrenergic innervation of the meninges at the time of birth is not responsible for the termination of the proenkephalin gene expression.
脑膜成纤维细胞在胚胎发育期间表达前脑啡肽原基因，但在出生前不久终止表达。在出生后第1天进行原代培养时，成纤维细胞再次表达该基因。蛋白激酶A的激活降低了这种表达，因此可能导致其在产前终止。由于脑膜的去甲肾上腺素能神经支配在出生前后开始，本研究调查了肾上腺素能激动剂如何影响培养的成纤维细胞中前脑啡肽原mRNA的水平。β2-肾上腺素能受体激动剂沙丁胺醇和丙卡特罗增加了内源性cAMP的水平，并降低了前脑啡肽原mRNA的浓度，表明培养的成纤维细胞具有这种β亚型。相反，去甲肾上腺素以浓度依赖的方式增加了前脑啡肽原mRNA的水平。这种作用不依赖于内源性cAMP，而是由α1-肾上腺素能受体介导的。数据表明，出生时脑膜的去甲肾上腺素能神经支配与前脑啡肽原基因表达的终止无关。
